Deficiency of N-myristoylation reveals calcineurin activity as regulator of IFN-γ-producing γδ T cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Bonrouhi, Mahnaz¹  Krunic, Damir¹  Grö¹  Popovic, Zoran V.²  Federico, Giuseppina⁴  Porubsky, Stefan⁴  Brunk, Fabian⁵  ne, Hermann-Josef⁶ 

[1] and;..Institute of Pathology, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany;Department of Cellular and Molecular Pathology, German Cancer Research Center, Heidelberg, Germany;Division of Developmental Immunology, German Cancer Research Center, Heidelberg, Germany;Light Microscopy Facility, German Cancer Research Center, Heidelberg, Germany

关键词: CD27+ γ    δ    T cells;    Calcineurin‐;    Nfatc pathway;    IL‐;    17A;    IFN‐;    γ   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

γδ T cell subsets can be characterized, in part, by their secretion of select proinflammatory cytokines. The molecular mechanisms driving the diverse fates of γδ T cells have not been elucidated. We have previously shown that the attachment of myristic acid to the N-terminal glycine of proteins, termed N-myristoylation, is essential for αβ T cell development and activation. Here, we explore the potential role of this lipid modification on the activation of γδ T cells. In the absence of N-myristoylation, the CD27⁺ γδ T cell subset was dominantly affected. The cells produced high levels of IFN-γ upon stimulation. In addition, they were more sensitive to inhibition of the CaN-Nfat pathway than were γδ T cells with myristoylated CaN. N-Myristoylation was found to modulate activity of phosphatase CaN, a regulator of Nfat. In summary, the CaN–Nfat pathway regulates development and function of IFN-γ-producing γδ T cells, and its balanced activity is strongly dependent on CaN N-myristoylation.

【 授权许可】

CC BY